1. Field of the Invention
The invention generally relates to the prevention and treatment of liver disease or damage. In particular, the invention provides methods of providing the sulfated oxysterol 25-hydroxycholesterol-3-sulfate (25HC3S) to a subject in order to prevent or treat liver disease or damage such as nonalcoholic fatty liver disease (NAFLD), to facilitate recovery after hepatectomy surgery and to promote lipid homeostasis.
2. Background of the Invention
The liver is a vital organ present in vertebrates and some other animals. This organ plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, hormone production, the maintenance of lipid homeostasis, detoxification, and production of biochemicals necessary for digestion. As a result of the wide-ranging and vital functions of this organ, subjects with liver disease or damage can experience drastic and debilitating health consequences. Although liver dialysis can be used in the short term, there is currently no way to compensate for the long term absence of liver function.
Damage to the liver can occur due to and/or be associated with a variety of factors such as exposure to various toxins, excessive consumption of alcohol, obesity, high fat diets, viral infections, hereditary factors, cancer, the long-term use of certain medications, trauma as the result of an accident or combat, etc. One particular liver disease that is currently of major concern is nonalcoholic fatty liver diseases (NAFLD). NAFLD is characterized by the accumulation of lipids (e.g. triglycerides) in liver tissue. This syndrome is associated with obesity and is currently estimated to affect almost one-quarter of the general United States population. The spectrum of NAFLD ranges from simple nonprogressive steatosis to progressive steatohepatitis (NASH) that is characterized by inflammation and results in liver cirrhosis and hepatocellular carcinoma. Lowering triglyceride levels and anti-inflammatory responses are important elements of successful NAFLD prevention and therapy. However, this option is unlikely to be adopted by many individuals in the developed world. A large number of medical treatments for NAFLD have been studied and, while many appear to improve biochemical markers such as alanine transaminase levels, most have not been shown to reverse histological abnormalities or reduce clinical endpoints.
Currently, the only long-term option for treating severe liver damage is liver transplantation, which may involve receipt of an entire organ from a deceased donor, or receipt of a lobe or liver tissue donated by a live donor. While transplantation can be successful, especially in view of the compensatory growth capabilities of liver tissue, the procedure is drastic, requiring major surgery and subsequent monitoring and treatment to avoid rejection.
There is obviously a need in the art to develop techniques to prevent or treat liver damage such as that which results from NAFLD, or from other causes, and to promote lipid homeostasis.